Abstract P2-11-19: Inflammatory indexes as prognostic biomarkers in advanced triple negative breast cancer patients
Authors: Caterina Gianni, Michela Palleschi, Emanuela Scarpi, Filippo Merloni, Eva Blondeaux, Fabio Puglisi, Elena Collovà, Palma Pugliese, Francesco Cognetti, Irene Giannubilo, Tommaso Ruelle, Claudia Bighin, Lucia Del Mastro, Ugo De Giorgi
Journal: Cancer Research (2023)

Abstract Background The identification of treatment selection biomarkers for advanced triple negative breast cancer (aTNBC) patients remains an unmet need. The immune system is known to be involved in the microenvironment of triple negative breast cancer (TNBC). Immune ratios like the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-lymphocyte ratio (MLR) and the systemic immune-inflammation index (SII) may reflect the immune system functional status in these patients and the involvement of circulating immune cells in cancer progression. In particular MLR showed to predict overall survival (OS) in aTNBC and to contribute to migration of circulating tumor cells [1]. Methods A retrospective-prospective, observational multicenter study from the GIM-14 experience was performed to investigate the association between inflammatory indexes (NLR, MLR, PLR and SII), as measured at baseline and at progression, and clinical and survival aspects in patients with aTNBC in first line setting. The optimal cutoff values between low and high expression of inflammatory indexes were established on the basis of cut-off values determined in a previously conducted study in order to validate them[1], and was used to predict progression-free survival (PFS) and OS. Time-to-event variables (PFS; OS) were calculated using Kaplan-Meier method, while Cox regression model was used to estimate HRs and their 95% CI. Results 105 consecutive patients with a diagnosis of aTNBC were fully evaluated for the final analysis. The median age at diagnosis was 55 years (33-86). Of them, 80 patients received a neo/adjuvant treatment after diagnosis. At first progression the majority of patients (n= 97) received chemotherapy, while only 8 patients were treated with chemo-immunotherapy due to the programmed death ligand 1 (PD-L1) expression in the immunohistochemical analyses. At a median follow-up of 54 months, median PFS in the whole patients population was 13 months (95% CI 9,4-16,5), while median OS was 17.3 OS (95% CI 13-22,2). All high inflammation based scores evaluated at diagnosis of metastatic disease were significantly associated with lower PFS, in particular high NLR (≥3) and high MLR (≥0.34) (p = 0.0006 and p = 0.011, respectively). Similarly, all high indexes appeared significantly associated with a lower OS, especially NLR (&amp;gt;3), SII (≥836) and MLR (≥0.34) (p &amp;lt; 0.0001, p = 0.0005, p=001 respectively). In particular also NLR and SII evaluated at disease progression after first line treatment were significantly associated with a worse OS (p=0.0006 and p=0.001 respectively). In multivariable analysis for predictors of overall survival, the number of metastatic sites, NLR, SII and MLR remained significant (p&amp;lt; 0.0001, p=0.006, p=0.005 respectively). Conclusions NLR, SII and MLR are predictors of OS in aTNBC. Although our results need validation with larger studies, we suggest that inflammatory ratios could be used as feasible biomarkers of prognosis and treatment efficacy in aTNBC. Further research about HER-2 low categorized patients will be updated and presented at the final meeting. 1. De Giorgi U, Mego M, Scarpi E, Giordano A, Giuliano M, Valero V, Alvarez RH, Ueno NT, Cristofanilli M, Reuben JM. Association between circulating tumor cells and peripheral blood monocytes in metastatic breast cancer. Ther Adv Med Oncol. 2019 Aug 14;11:1758835919866065. doi: 10.1177/1758835919866065. PMID: 31452692; PMCID: PMC6696837. Citation Format: Caterina Gianni, Michela Palleschi, Emanuela Scarpi, Filippo Merloni, Eva Blondeaux, Fabio Puglisi, Elena Collovà, Palma Pugliese, Francesco Cognetti, Irene Giannubilo, Tommaso Ruelle, Claudia Bighin, Lucia Del Mastro, Ugo De Giorgi. Inflammatory indexes as prognostic biomarkers in advanced triple negative breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-19.